Antibody-Drug Conjugates
Constructive.bio produces homogeneous antibody-drug conjugates with defined drug-antibody ratios (DAR) of exactly 2 or 4 through site-specific ncAA incorporation and bio-orthogonal click chemistry. This eliminates the heterogeneous mixtures (DAR 0–8) produced by conventional cysteine or lysine conjugation, delivering batch-to-batch consistency that reduces toxicity and improves therapeutic index.
The Problem
Traditional ADC manufacturing conjugates cytotoxic payloads to native cysteine or lysine residues, producing mixtures with 0–8 drugs per antibody. This heterogeneity causes batch variability, unpredictable pharmacokinetics, and increased toxicity from over-loaded species. Under-loaded species reduce efficacy while contributing to immunogenicity. No conventional approach can guarantee a precise, reproducible DAR across manufacturing batches.
Our Approach
Constructive.bio incorporates ncAAs bearing bio-orthogonal reactive handles — azide (for SPAAC click chemistry) or tetrazine (for inverse electron-demand Diels-Alder) — at genetically defined positions in the antibody sequence. These handles react selectively with complementary groups on the payload-linker, achieving conjugation at exact sites with no off-target modification. The result is a homogeneous ADC population with defined DAR, consistent drug placement, and reproducible manufacturing. Our platform supports multiple conjugation chemistries and payload classes including auristatins, maytansinoids, and PBD dimers.
Key Capabilities
Defined DAR of exactly 2 or 4 — no heterogeneous mixtures
Site-specific conjugation via azide-SPAAC or tetrazine-iEDDA click chemistry
Compatible with multiple payload classes: auristatins, maytansinoids, PBD dimers
Batch-to-batch DAR consistency eliminates over-loaded toxic species